ALDH2 Human

Aldehyde Dehydrogenase-2 (ALDH2) is a crucial enzyme in the human body, primarily involved in the metabolism of aldehydes. It plays a significant role in detoxifying acetaldehyde, a toxic byproduct of alcohol metabolism, by converting it into acetic acid. This enzyme is predominantly found in the mitochondria and is essential for maintaining cellular health and preventing the accumulation of harmful aldehydes.

ALDH2 is encoded by the ALDH2 gene, which has several genetic variants. One of the most well-known variants is the rs671 polymorphism, commonly found in East Asian populations. This variant results in an inactive form of the enzyme, leading to the accumulation of acetaldehyde after alcohol consumption. This accumulation causes the characteristic “alcohol flush reaction,” which includes symptoms such as facial flushing, nausea, and rapid heartbeat .

Recent studies have identified additional ALDH2 variants, such as rs747096195 (R101G) and rs190764869 (R114W), which also lead to inefficient acetaldehyde metabolism and similar physiological responses . These variants have been characterized using human recombinant ALDH2 proteins and biochemical assays, revealing their reduced enzymatic activity and impaired dimer/tetramer formation .

The deficiency or inactivity of ALDH2 due to genetic variants is associated with an increased risk of several diseases, including esophageal cancer, cardiovascular diseases, and alcohol-related liver diseases . The accumulation of acetaldehyde and other toxic aldehydes can cause oxidative stress and damage to cellular components, contributing to the development of these conditions.

Research has shown that enhancing ALDH2 activity through post-translational modifications, such as phosphorylation by epsilon protein kinase C (εPKC), can provide protection against aldehyde-induced toxicity . This has opened up potential therapeutic avenues for conditions related to ALDH2 deficiency. For instance, pharmacological activation of ALDH2 has been explored as a strategy to mitigate the effects of myocardial infarction, stroke, and other oxidative stress-related diseases .

Human recombinant ALDH2 is produced using recombinant DNA technology, which involves inserting the ALDH2 gene into a suitable expression system, such as bacteria or yeast. This allows for the large-scale production of the enzyme for research and therapeutic purposes. Recombinant ALDH2 has been used in various studies to understand the enzyme’s structure, function, and the impact of genetic variants .

The availability of recombinant ALDH2 has also facilitated the development of assays to screen for potential ALDH2 activators and inhibitors. These assays are crucial for identifying compounds that can modulate ALDH2 activity and potentially serve as therapeutic agents for diseases associated with ALDH2 deficiency .